Sensing Reactive Oxygen and Nitrogen Species Using Selective Fluorescent Probes
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Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generally thought to be important mediators of various pathological conditions. Since fluorescent probes are promising tools for clarifying the functions of biomolecules in biological systems as demonstrated by the case of Ca2+ fluorescent probes, interest in the use of fluorescent probes for sensing ROS/RNS is increasing. Although fluorescent probes such as 2,7-dichlorodihydrofluorescein (DCFH) and dihydrorhodamine 123 (DHR123) have traditionally been used for sensing ROS/RNS, many reports suggest that such probes are not suitable for sensing specific ROS/RNS individually but for whole oxidative stresses caused by ROS/RNS due to their lack of selectivity for ROS/RNS. However, it is quite important to detect specific ROS/RNS with a high selectively because each ROS/RNS has its own physiological activities and has unique characteristic roles. To achieve such specificity, novel functional fluorescent probes that can distinguish specific ROS/RNS individually with high selectivity, have been developed in recent years. The purpose of this review is to highlight recent advances in the design and development of such selective ROS/RNS fluorescent probes that should have a great potential for evaluating the unique roles of individual ROS/RNS in biological processes. Keywords: Fluorescent probe, reactive oxygen species (ROS), reactive nitrogen species (RNS), molecular imagingKeywords:
Reactive nitrogen species
Biomolecule
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generally thought to be important mediators of various pathological conditions. Since fluorescent probes are promising tools for clarifying the functions of biomolecules in biological systems as demonstrated by the case of Ca2+ fluorescent probes, interest in the use of fluorescent probes for sensing ROS/RNS is increasing. Although fluorescent probes such as 2,7-dichlorodihydrofluorescein (DCFH) and dihydrorhodamine 123 (DHR123) have traditionally been used for sensing ROS/RNS, many reports suggest that such probes are not suitable for sensing specific ROS/RNS individually but for whole oxidative stresses caused by ROS/RNS due to their lack of selectivity for ROS/RNS. However, it is quite important to detect specific ROS/RNS with a high selectively because each ROS/RNS has its own physiological activities and has unique characteristic roles. To achieve such specificity, novel functional fluorescent probes that can distinguish specific ROS/RNS individually with high selectivity, have been developed in recent years. The purpose of this review is to highlight recent advances in the design and development of such selective ROS/RNS fluorescent probes that should have a great potential for evaluating the unique roles of individual ROS/RNS in biological processes. Keywords: Fluorescent probe, reactive oxygen species (ROS), reactive nitrogen species (RNS), molecular imaging
Reactive nitrogen species
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Reactive nitrogen species
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Reactive oxygen species are reactive, partially reduced derivatives of molecular oxygen (O2). Important reactive oxygen species in biologic systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Closely related species include the hypohalous acids, particularly hypochlorous acid; chloramine and substituted chloramines; and singlet oxygen. Reactive nitrogen species are derived from the simple diatomic gas, nitric oxide. Peroxynitrite and its protonated form, peroxynitrous acid, are the most significant reactive nitrogen species in biologic systems. A variety of enzymatic and nonenzymatic processes can generate reactive oxygen species and reactive nitrogen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species and reactive nitrogen species are important in the pathogenesis of acute respiratory distress syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species–mediated or reactive nitrogen species–mediated stress with the development of acute respiratory distress syndrome. Despite these data, pharmacologic strategies directed at minimizing reactive oxygen species–mediated or reactive nitrogen species–mediated damage have yet to be successfully introduced into clinical practice. The most extensively studied compound in this regard is N-acetylcysteine; unfortunately, clinical trials with this compound in patients with acute respiratory distress syndrome have yielded disappointing results.
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Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction in molecular oxygen. Four major ROS are recognized comprising superoxide (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen ((1)O2), but they display very different kinetics and levels of activity. The effects of O2•- and H2O2 are less acute than those of •OH and (1)O2, because the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and nonenzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or (1)O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics and nonpharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma, and medicinal honey. A brief final section covers reactive nitrogen species and related therapeutics, such as acidified nitrite and nitric oxide-releasing nanoparticles.
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In various reactive oxygen species (ROS)-based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS-based antitumor outcomes is not even explored yet. To address it, a photocleaved O2 -released nanoplatform is constructed to release and switch ROS into reactive nitrogen species (RNS) for repressing hypoxic breast tumor. Systematic explorations validate that the nanoplatforms can attain continuous photocontrolled O2 release, alleviate hypoxia, and elevate ROS level. More significantly, the entrapped PDE5 inhibitor (PDE5-i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Intriguingly, ROS conversion into RNS can help ROS to evade the hypoxia-induced resistance to ROS-based antitumor. Eventually, RNS production unlocks robust antitumor performances along with ROS elevation and hypoxia mitigation. Moreover, this extraordinary conversion from ROS into RNS also can act as a general method to solve the short lifetime of ROS.
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Production of reactive oxygen species (ROS) during host-pathogen interactions is termed oxidative burst. The most important ROS include singlet oxygen (1O2), superoxide anion O2-., the hydroxyperoxyl radical (HO2·), hydrogen peroxide (H2O2) and the hydroxyl radical (·OH). Nitric oxide (NO), which has a close relation with the ROS, belongs to reactive nitrogen species (RNS). The ROS and NO are involved in regulation of plant growth and development and in responses to environmental stress, and play an important role especially in their defense against pathogenic invasion. Different roles of the ROS and NO in host-pathogen interactions are discussed.
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Reactive oxygen and nitrogen species (ROS and RNS respectively) play an important role in the proper functioning of many cellular processes. Generation of reactive oxygen species is an integral part of aerobic metabolism of cells. Their overproduction and subsequent oxidative stress occurs during pathogenesis of many diseases. Nitrosative stress is very closely linked to oxidative stress. Nitric oxide (NO), can react with molecular oxygen, superoxide anions and metal cations generating consecutive reactive oxygen species. These highly reactive chemical compounds react with proteins impairing their function by oxidation, or nitrosylation of amino acid residues, which may induce apoptosis. Furthermore, nitric oxide enhances the effect induced by cyclooxygenases and becomes a mediator of the inflammatory response. This paper gathers key information on the reactive oxygen and nitrogen species as well as processes in which they participate.
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Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated as contributing to the pathogenesis of a broad spectrum of diseases [1, 2]. Historically, oxygen free radicals were primarily considered to be aggressive species, indeed the superoxide (O 2 .- theory of oxygen toxicity is based on this hypothesis, (reviewed in 3). There is circumstantial evidence to support this view, some of which will be reviewed elsewhere in this chapter. However, other roles for free radicals — or more appropriately ROS and RNS — have recently emerged, most notably as signal or second messenger molecules. It seems therefore that these species can have differing effects which are dependent on their levels of production and on antioxidant defences. This chapter will mainly be concerned with the deleterious consequences associated with these reactive species, particularly in the lung, with special reference to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
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Oxygen toxicity
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ROS (reactive oxygen species) and RNS (reactive nitrogen species) are central to the innate immunity that protects us from infection, but also contribute to degenerative diseases and possibly aging. However, ROS and RNS are increasingly recognized to contribute to physiological signalling. This review briefly describes the main interactions between ROS and RNS and shows how their origins, chemistry, metabolism and biological actions are intimately linked.
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